1. Field of the Invention
The present invention relates to a novel thrombin-binding substance associated with fibrinolytic or anticoagulation systems. More particularly, this invention relates to a thrombin-binding substance, which is useful as a medicine especially in the treatment of thrombosis, and to a method for the production of this substance.
2. Description of the Prior Art
Extensive work has been devoted to thrombin which plays an important role as a proteolytic enzyme in the mechanism to control clotting (blood coagulation) in the organism, and a great deal of knowledge has been accumulated to clarify the mechanism by which the thrombin operates.
N. L. Esmon et al. have recently reported that thrombin accelerates the activation of protein C which presumably acts on the fibrinolytic and the anticoagulant systems. They reported the presence of a certain substance in extracts of rabbit lung tissue functioning as a coenzyme for such activation mechanism, and named it thrombomodulin (J. Biological chemistry, 257(2)859-864, 1982).
Aoki, one of the inventors, and others also separated human thrombomodulin from human placenta. The substance had similar properties with that reported by N. L. Esmon et al., with a molecular weight of about 71,000 in a unreduced condition (Thromb. Res. 37, 353-364, 1985).
Furthermore, I. Maruyama et al. separated human thrombomodulin from human placenta with a molecular weight of about 75,000, and compared it with the rabbit thrombomodulin stated above to find that both had identical activities (J. Clin, Invest. 75, 987-991, March 1985).